ABSTRACT Both alcohol misuse and HIV infection increase the risk for bacterial pneumonia, but the explanation for this increased risk is unknown. Preliminary data from our laboratory implicate changes in the gut microbiome (dysbiosis). We hypothesize that host susceptibility to bacterial pneumonia in alcohol-misusing and HIV-infected subjects is mediated through intestinal dysbiosis and changes in sIgA coating of specific bacterial groups. We will study human subjects and use a unique fecal transplant model where human fecal samples are xenotransplanted into mice. There are 2 Specific Aims. SA1 will address dysbiotic sIgA-coated bacteria as they influence host responses to a lung infectious challenge. SA2 will investigate the Mucosal-Associated Invariant T (MAIT) cell population of as an immune link between alcohol-induced dysbiosis and impaired host defense against pneumonia. This project will uncover mechanisms through which changes in gut microflora influence host responses to pulmonary infection (the gut-lung axis) and will lead to new knowledge as to how alcohol and HIV infection impair immunity in the lung.